Sensory-evoked synaptic network discharges recorded in the dorsal horn regions of fetal mouse spinal cord explants with attached dorsal root ganglia (DRGs) can be selectively depressed by exposure to analgesic concentrations of morphine, other opiates, and endorphins. These depressant effects are reversed by naloxone as in situ. High stereo-specific opiate receptor binding levels have been demonstrated in these cultures, especially in the DRG neurites. Furthermore, enhancement of sensory-evoked cord responses by low levels of naloxone in cultures not previously exposed to exogenous opiates suggest that these sensory CNS networks may also develop localized opiate inhibitory control systems mediated by CNS endorphins, e.g. enkephalins. This new tissue culture model will be utilized to analyze some of the mechanims underlying the physiologic effects of acute as well as chronic exposure to opiates and endorphins, including studies of the role of calcium ions and cyclic AMP in opiate effects on CNS functions, and development of tolerance and dependence. Cellular localization of opiate receptors and enkephalins in spinal cord-DRG explants and in cultures of isolated DRG or cord neurons will be closely correlated with functional analyses. Studies of opioid neural networks in cord-DRG explants will be extended to co-cultures of cord-DRG with explants of monaminergic brainstem tissues which may be involved in regulation of nociceptive opioid systems. Coordinated bioelectric and histofluorescence analyses of these monoaminergic pathways in culture may provide further insights into the development of the complex neural circuits regulating opioid networks of the spinal cord and brainstem. Similar techniques are being utilized in our current studies of aminergic neurons in explants of locus coeruleus and raphe tissues co-cultured with hippocampus. Correlative studies of opioid and aminergic networks in vitro may clarify some of the cellular mechanisms linking these important neural control systems in situ.